Magnesium and calcium stearates have long been recognized in the art of pharmaceutical compounding as lubricants and are probably the most common pharmaceutical lubricants in use at the present time. These substances, however, in spite of their wide acceptance in the pharmaceutical arts as lubricants have certain disadvantages.
The primary disadvantage to the use of magnesium and calcium stearate as pharmaceutical lubricants lies in the fact that they are extremely hydrophobic. This hydrophobicity hinders dissolution and disintegration time of solid dosage forms containing magnesium and calcium stearates. Another factor which acts to hinder dissolution and disintegration time of solid dosage forms containing magnesium or calcium stearate is their electrostatic attraction with therapeutically active substances and other excipients. This electrostatic attraction is particularly pronounced when calcium and magnesium stearate are utilized in finely divided particulate form, i.e., an average particle size in the range of from 1 to 15 microns. This disadvantage of magnesium and calcium stearates is not uncommon, however, as there are in the literature numerous reports of other common pharmaceutical excipients inhibiting the dispersion of particles of active drug in the gastric media as a result of hydrophobicity. Other commonly utilized pharmaceutical compounding excipients act to impede dissolution in various ways in addition to being hydrophobic such as, for example, by forming an insoluble film around the active drug particle or by chemically complexing the active drug particles.
One attempt which has been made to remedy the problems caused by the hydrophobicity of many pharmaceutical compounding excipients is the inclusion of surfactants into solid dosage forms containing them to improve dispersibility. Where surfactants are utilized, however, they are, for the most part, utilized in such minute quantities that homogeneous distribution throughout the dosage form is virtually impossible.
It has been suggested to form an itimate mixture of surfactants with certain acidic substances for incorporation into effervescent tablets. U.S. Pat. No. 3,151,986 discloses such mixtures wherein fumaric and adipic acid are "coated" with a surfactant prior to incorporation into effervescent tablets. It is stated therein that the "coated" particles of acid are more free-flowing during preparation of the tablets and are more soluble in water than uncoated particles. The "coating" of such particles, however, protects them until such time as they enter into the required acid-base reaction in the presence of water. In effervescent tablets, acid particles must in fact usually be protected within the tablet to prevent premature reaction with the base. It is therefore clear that such "coated" particle substrates have no positive function either of the preparation of the tablet or in the tablet itself and the substrates do not function until the "coating" is removed.
In view of the foregoing, it is considered unexpected that coating particles of magnesium or calcium stearate with a surfactant in accordance with the invention produces particles free of the disadvantageous hydrophobicity characteristic of these pharmaceutical lubricants in conventional uncoated form yet umimpeded in lubricant efficaciousness. The fact that magnesium or calcium stearate particles coated with a surfactant in accordance of the invention are equal to uncoated particles as pharmaceutical lubricants is particularly surprising when it is considered that the surfactants which are utilized to coat them exert a negative effect on lubricity when present in uncombined form.